AHRR (cg05575921) methylation extent of leukocyte DNA and lung cancer survival.
Aged
Basic Helix-Loop-Helix Transcription Factors
/ blood
Biomarkers, Tumor
/ blood
DNA Methylation
DNA, Neoplasm
/ blood
Disease-Free Survival
Female
Humans
Leukocytes
/ metabolism
Lung Neoplasms
/ blood
Male
Middle Aged
Neoplasm Proteins
/ blood
Prospective Studies
Repressor Proteins
/ blood
Smoking
/ blood
Survival Rate
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
18
10
2018
accepted:
26
01
2019
entrez:
8
2
2019
pubmed:
8
2
2019
medline:
7
11
2019
Statut:
epublish
Résumé
Prior studies have shown that AHRR (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if AHRR (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients. In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured AHRR (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of AHRR (cg05575921) methylation. We observed the expected inverse correlation between cumulative smoking and AHRR methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05-2.09), however, AHRR (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer. AHRR (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.
Sections du résumé
BACKGROUND
Prior studies have shown that AHRR (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if AHRR (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients.
METHODS
In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured AHRR (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of AHRR (cg05575921) methylation.
RESULTS
We observed the expected inverse correlation between cumulative smoking and AHRR methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05-2.09), however, AHRR (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer.
CONCLUSION
AHRR (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.
Identifiants
pubmed: 30730943
doi: 10.1371/journal.pone.0211745
pii: PONE-D-18-30222
pmc: PMC6366765
doi:
Substances chimiques
AHRR protein, human
0
Basic Helix-Loop-Helix Transcription Factors
0
Biomarkers, Tumor
0
DNA, Neoplasm
0
Neoplasm Proteins
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0211745Déclaration de conflit d'intérêts
The salary of Katja Kemp Jacobsen was funded by a Post doc grant from Lundbeck Foundation. This funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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